Allergic reactions in oral and perioral diseases-what do allergy skin test results show?

OBJECTIVE: The aim of this study was to examine potential allergic reactions to different materials in oral and perioral diseases. STUDY DESIGN: The study included 230 consenting subjects in total-180 patients with oral and perioral diseases (30 patients each in the following groups: angioedema, oral lichenoid reactions [OLRs], burning mouth syndrome [BMS], gingivostomatitis, cheilitis, and perioral dermatitis) and 50 healthy controls. Comprehensive diagnostic workups were performed prior to patch testing with standard series allergens and with specific dental materials and skin prick testing (SPT) for food, preservatives and additives, and inhalants. RESULTS: Positive allergy test results were more common in patients with oral diseases than in controls, with significantly greater frequency of contact allergies in the cheilitis group (P = .048). The most common allergens in the majority patients were cobalt chloride (13.3% in BMS vs 10% in controls) and nickel sulfate (10% in gingivostomatitis and 6.7% in cheilitis vs 3.3% in controls), and preservatives (23.3% in angioedema and BMS). CONCLUSIONS: Allergy skin tests are reliable and justified for diagnosing allergies in cases of persistent or recurrent oral diseases. This is the only way to confirm allergies and is the basis for consequent allergen avoidance for the benefit of the patient.

Phagocytic functions of salivary neutrophils in oral mucous membrane diseases.

BACKGROUND AND PURPOSE: Phagocytic functions of salivary polymorphonuclear neutrophils (sPMNs) have not been comprehensively studied in patients with oral mucous membrane diseases, although available data suggest the role of immunity in their pathogenesis. SUBJECTS AND METHODS: Phagocytic functions of sPMN were determined in 15 patients with acute recurrent aphthous ulceration (RAU), 11 patients with oral lichen planus (OLP) and 20 healthy volunteers. In healthy subjects, the same parameters were also determined in peripheral blood polymorphonuclear neutrophils (bPMNs). Phagocytic activity (proportion of ingesting cells, PA), ingestion ability (number of ingested targets per 100 phagocytes, IA) and intracellular microbicidity (proportion of killed targets, IM) of PMNs separated from peripheral blood and the whole unstimulated saliva were determined by acridine orange method with living yeast cells as targets. RESULTS: Salivary PMNs in healthy individuals showed significant reduction in PA (33% vs. 76%; P < 0.009) and IA (0.47% vs. 2.93%; P < 0.009) and significant increase in IM (12.0% vs. 5.5%; P = 0.011) in comparison with bPMNs. In RAU patients, reduced PA (27% vs. 37%; P = 0.035) and IA (0.25% vs. 0.47%; P = 0.05) were detected, while in OLP patients enhanced IM was detected (12% vs. 19%; P = 0.033) in comparison with healthy controls. CONCLUSION: Salivary PMNs present functional features distinct from those in peripheral blood. Some phagocytic functions of sPMNs are reduced in RAU and enhanced in OLP, indicating their role in pathogenesis or reflecting clinical changes in these conditions.

Salivary levels of vascular endothelial growth factor (VEGF) in recurrent aphthous ulceration.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic cytokine involved in angiogenesis and wound healing. Its presence in recurrent aphthous ulceration has not been reported to date. The aim of this study was to investigate the association of salivary levels of VEGF with various stages of recurrent aphthous ulceration (RAU). METHODS: VEGF levels were determined in a group of 27 age and sex-matched healthy controls and in 30 patients with minor and major RAU grouped into the three stages: (I) early active stage, (II) active stage, and (III) remission period. VEGF levels (pg/ml; mean +/- SD) in unstimulated whole saliva were determined by enzyme immunoassay. RESULTS: Patients with major RAU - stages I and II - had decreased VEGF values (765 +/- 458 and 341 +/- 109, respectively) when compared both to healthy controls (1652 +/- 567; P < 0.01) and to stage III major RAU (1524 +/- 784; P < 0.005). CONCLUSION: Salivary VEGF levels seemed to be associated with ulcer development in major RAU, showing stage-dependent alterations during the course of this disorder.

Helicobacter pylori colonization of tongue mucosa--increased incidence in atrophic glossitis and burning mouth syndrome (BMS).

Nested polymerase chain reaction (PCR) was performed to detect the presence of Helicobacter pylori in tongue mucosa in 268 patients divided into four groups according to their diagnosis: 87 with atrophic glossitis, 37 with benign migratory glossitis and 144 with burning mouth syndrome (BMS). The latter group was subdivided according to anatomic site of burning sensation: subgroup A (54 patients) with complaints limited to tongue and subgroup B (90 patients) with burning sensations in other parts of oral mucosa. H. pylori was found in 43 samples (16%). Bacteria were significantly less present in tongue mucosa affected with benign migratory glossitis compared with atrophic glossitis and BMS (P=0.025). This difference was more obvious when compared with atrophic glossitis only (P=0.006). Mucosal changes in these conditions might make the oral environment more acceptable for H. pylori colonization compared with normal mucosa, and this mechanism may play a role in its oro-oral transmission.

Xerostomia in patients with triple A syndrome--a newly recognised finding.

Triple A syndrome is characterised by achalasia, alacrima, adrenal insufficiency and progressive neurological abnormalities including impaired autonomic nervous function. We present five patients with triple A syndrome in whom we describe xerostomia for the first time, a symptom which was presumed to be practically exclusive to Sjøgren syndrome and familial dysautonomia. Conclusion We recommend the investigation of salivation in all patients with triple A syndrome and treatment of xerostomia in order to ease swallowing. Further, our results corroborate earlier doubts that some patients with Sjøgren syndrome, especially those with the so-called "achalasia sicca" syndrome and adrenocortical insufficiency, actually had triple A syndrome. Therefore, adrenocortical function should be assessed in all patients with Sjøgren syndrome, particularly in those with difficulties in swallowing, because even latent adrenocortical insufficiency could be life-threatening for these patients in stressful situations.

Synthesis and reactivity of the monosaccharide esters of amino acids as models of teichoic acid fragment.

The increasing prevalence of sepsis from gram-positive bacterial pathogens necessitates further evaluation of the basic assumptions about the molecular pathogenesis of septic shock. Since diverse physiological functions of gram-positive bacteria are controlled by the degree of esterification of teichoic acids with D-alanine, we examined the reactivity of monosaccharide esters in which anomerically free or protected D-glucose is linked through its C-6 hydroxy group to either phenylalanyl or tyrosyl residues as models for teichoic acid fragment. We show that the attached sugar moiety induces activation of the amino acid residue. Due to the enhanced reactivity of the NH2 group in the monosaccharide esters studied, the formation of products generated by intramolecular and intermolecular glycation reactions is accelerated resulting in heterogeneous mixture of compounds. These findings suggest that, if similar adducts are formed by glycation of D-alanine in teichoic acid of gram-positive bacteria, they should be examined as potential bioactive ligands or chemical message for infection.

A retrospective analysis of 96 "asp" (Megalopyge opercularis) envenomations in Central Texas during 1996.

BACKGROUND: The most frequently reported caterpillar envenomation in Central Texas is by the puss caterpillar or "asp," Megalopyge opercularis. This caterpillar is described by patients and physicians as inflicting intense radiating pain. The intensity of symptoms may be underestimated leading to undertreatment. Adequate treatment protocols have been lacking and those in use are not very successful. We present a retrospective study of patients who were stung and contacted the Central Texas Poison Center. METHODS: All human exposures to asp stings reported to the Central Texas Poison Center during 1996 were included. Inclusion criteria consisted of all cases documented as an asp envenomation by the specialists in poison information. Characterization of symptoms and treatment used were evaluated. RESULTS: There were 96 exposures to asps reported. Ninety-five of the patients experienced local pain with 26 of these reporting intense radiating pain. Forty developed erythema, 27 described edema, and 9 complained of welts/hives. Other symptoms reported included white spots (4), pruritus (3), red streak (2), numbness (2), and individual accounts of chest pain, rash, ecchymosis, tingling, blister, and muscle spasm. There was no treatment modality that promptly relieved pain. DISCUSSION: Although asp envenomations appear to be very common, clinical cases have rarely been documented. This may be due to physicians not recognizing the etiological agent. Pain may be very intense and standard pain management appears to be unsuccessful. CONCLUSION: This study suggests that further examination of treatment modalities may be beneficial in addressing the morbidity of Megalopyge opercularis envenomations.

The p53 and nm23-H1 genes are not deleted in oral benign epithelial lesions.

In an effort to identify genetic changes that may be the early hallmarks of epithelial cell overproliferation, we searched for p53 and nm23-H1 allelic deletions in oral benign epithelial lesions. In the study group were 25 benign epithelial lesions (lichen planus--17; leukoplakia--8; recurrent aphthous ulcers--2; one specimen diagnosed as benign migratory glossitis). Among 21 samples analysed for exon 4 (p53 gene) LOH, only 6 were informative, with no loss of either allele. OF 23 samples tested for LOH at intron 6 of p53 gene, 8 were informative, again with no presence of LOH. For nm23-H1 gene, the analysis was performed on a total of 24 cases. Of them, 16 were informative, however, none exhibited LOH at this locus. In conclusion, whereas the presence of gross gene alterations (LOH) would have been definitive evidence for the involvement of p53 and/or nm23 in the hyperproliferation process, the absence of LOH does not exclude the presence of either smaller mutations, altered regulation of normal gene, or dysfunction at the level of wild type protein. Alternatively, p53 and nm23-H1 may have no relation to oral lesion formation, and cannot presently be considered as an early step in benign, tissue transformation.

Detection of Helicobacter pylori in various oral lesions by nested polymerase chain reaction (PCR).

Nested PCR was used for the detection of Helicobacter pylori DNA in specimens collected from seven different topographic sites in the oral cavity. Out of 161 patients, only 21 (13.04%) were positive. There was no correlation between H. pylori status and patient diagnosis and age. No preferential site for bacterial colonization was found in the oral cavity, nor was an association established between a bacterial presence and ulcerated versus non-ulcerated lesions. The results indicate that the oral mucosa does not appear to represent a preferred site of colonization for H. pylori. Furthermore, the evidence presented in this paper suggests that H. pylori is not pathogenic in the oral cavity, nor is it associated with common oral pathologic processes.

Reduction of epithelial dendritic cells in keratotic lesion of oral lichen planus.

The number and distribution of epithelial dendritic cells (EDC) in oral mucosal lesions are variable depending on the degree of epithelial maturation/differentiation and disease activity. Localized absence of EDC might impair mucosal immunologic protection, allow microbial colonization and enhance carcinogenesis. Increased number of EDC during the early stage of oral lichen planus (OLP) suggests their increased antigen-presenting capability and immunologic activity with inflammatory reaction, but their role in the process of keratinization remains unclear. Therefore, the purpose of this study was to determine the number and distribution of EDC in 33 biopsy specimens from lesions of OLP and from 18 control specimens of leukoplakia (LPL) at sites undergoing increased keratinization. Cells were identified immunocytochemically by the presence of antigen CD68 and labeled with acid phosphatase (AP) and alpha-naphthyl acetate esterase (ANAE) techniques. Numbers of EDC were expressed per mm epithelial surface length. Significantly more EDC with prominent histoenzymatic activity of AP and ANAE were present in OLP than in LPL. Intense enzymatic activity of ANAE was expressed in EDC of OLP with hyperparakeratosis. In the lesions with increased keratinization the number of EDC was markedly reduced in OLP while in LPL remained unchanged. Reduced number and subbasal redistribution of EDC in OLP suggest diminution of immunologic reaction and disease activity but also increased tissue vulnerability to various antigen challenges.

Interleukin-1 alpha induces corticotropin-releasing factor secretion and synthesis from NPLC-KC cells through various second messenger pathways.

Interleukin-1 (IL1) is a key messenger implicated in endocrine and immune systems that interact to mediate the stress response. Corticotropin-releasing factor (CRF) secretion and synthesis in the NPLC-KC human hepatoma cell line has been shown to respond to IL1 stimulation. We have studied how various inhibitors of second messenger pathways alter this IL1 effect. NPLC-KC cells were grown in six-well Costar plates and treated for 12 or 24 h with or without 500 pM IL1 (alpha form) in the presence of various inhibitors of second messenger pathways. Inhibitors included the protein kinase C (PKC) inhibitor, H-7; the protein kinase A inhibitor, IP20; or the cyclooxygenase inhibitor indomethacin (IND). Both cell extracts and secretion media were assayed for CRF-like immunoreactivity by radioimmunoassay. IP20, H-7, and IND all reduced basal CRF secretion at 24 h but not at 12 h. No effects were seen on basal CRF synthesis with these inhibitors. The three inhibitors also reduced IL1 effects on CRF secretion at 12 and 24 h. The reduction seen with all three inhibitors was statistically significant (P < 0.05) at 12 h. Although a reduction was seen with all three inhibitors at 24 h, a statistically significant reduction (P < 0.05) was demonstrable only for H-7. IL1 stimulated CRF synthesis in the NPLC-KC cells appears to only involve PKC pathways. Only the PKC inhibitor H-7 reduced the augmentation that IL1 produces on CRF synthesis. This effect was statistically significant at 12 and 24 h (P < 0.05).

The BE (2)-M17 neuroblastoma cell line synthesizes and secretes corticotropin-releasing factor.

The BE (2)-M17 human neuroblastoma has previously been shown to express corticotropin-releasing factor (CRF) mRNA following retinoic acid treatment. It is demonstrated in this report that both cell extracts and cell incubation medium of retinoic acid-treated BE (2)-M17 cells were shown to contain CRF-like immunoreactivity (CRF-LI) by RIA. CRF-LI secretion and content were also dose-dependently increased by forskolin. In addition, cell extracts were applied to a C18 Vydac column and peak CRF-LI from the collected fractions was shown to coincide in time of elution with peak immunoreactivity seen with oxidized synthetic CRF standard. Thus, in containing the CRF peptide, the BE (2)-M17 cells are useful models for further study of CRF cellular and genetic regulation.

Corticotropin-releasing factor is secreted in the BE(2)-C neuroblastoma cell and is responsive to forskolin.

The BE(2)-C human neuroblastoma has been shown to express corticotropin-releasing factor (CRF) messenger RNA. In this study, BE(2)-C cells were treated 5 days with 5 microM retinoic acid. Cell extracts were also applied onto a C18 Vydac column and fractions were assayed for CRF-like immunoreactivity (CRF-LI) which coincided in time of elution with oxidized or non-oxidized CRF synthetic CRF standard. With forskolin treatment, secretion media and cell extract CRF-LI increased in a concentration-dependent fashion. Thus, this cell line synthesizes and secretes CRF and is a good model for studying CRF regulation.

Natural killer cell activity in schizophrenia and schizoaffective disorder: a pilot study.

Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed.

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers. Of the indices of LHPA activity, only CSF CRF concentrations distinguished the four subject groups, with CSF CRF being significantly elevated in the more severely depressed major depression patients. Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers. These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity, at least as determined cross-sectionally. Further longitudinal studies with reference to diagnostic subtypes, severity, symptom profiles, and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations.

CSF 5-HIAA as a predictor of treatment response in trichotillomania.

Trichotillomania is characterized by chronic hair-pulling resulting in noticeable hair loss. In a preliminary study, cerebrospinal fluid (CSF) measures in 8 medication-free, female, trichotillomania patients were compared to those of matched, normal controls. There was no difference between patients and controls in measures of CSF cortisol, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). CSF measures did not correlate with measures of trichotillomania symptomatology. However, degree of response to treatment with serotonin re-uptake inhibitors significantly correlated with baseline CSF 5-HIAA. This suggests that central serotonin turnover is specifically relevant to treatment response to serotonin re-uptake inhibitors in trichotillomania.